1. Field of the Invention
The present invention relates to a novel process for producing 3-formylcyclopentanone derivatives. The 3-formylcyclopentanone derivatives produced by this process of the invention, have a substituent at the 2-position, and also have a formyl group at the 3-position, which can be converted to the other functional groups or substituents.
Due to their characteristic structures, the 3-formylcyclopentanone derivatives are remarkably useful as intermediates for producing physiologically active natural compounds, especially prostaglandins and derivatives thereof.
Other syntheses of prostanglandins from 3-formylcyclopentanone derivatives are known A. Greene and P. Crabbe; Tetrahedron Lett., 2215 (1975)!.
The present invention relates to a novel process for producing both these useful compounds and other novel compositions of matter which are necessary for the process of this invention.
2. Description of the Prior Art
Heretofore, for the purpose of producing prostaglandins and other related compounds, various synthetic methods using the cyclopentanone ring have been disclosed. Typical methods include:
(1) The Dieckmann reaction of alkyl adipate to produce 2-alkoxycarbonylcyclopentanones P. S. Pinkney, Org. Syntheses, Coll. Vol., 2, 116 (1943)!;
(2) The Aldol condensation of 1,4-dicarbonyl compounds to produce substituted cyclopentanones R. A. Ellison, Synthesis, 397 (1973)! and
(3) The Diels Alder reaction of substituted cyclopentadienes followed by oxidation and iodolactonization to produce the basic skelton of prostagrandin. E. J. Corey, et al., J. Amer. Chem. Soc., 93, 1489 (1971)!.
These processes in some ways have certain advantages. However, they are subject to several significant disadvantages: most of them can only be applied to the synthesis of simple systems; the selectivity of the reaction is very low in some cases; expensive or dangerous reagents are required; establishment of easy and operable conditions at some stages of the synthetic reactions is difficult; and purification of the products is difficult. Accordingly, these methods are generally not employed as industrial synthetic methods.
It has also been proposed to use bicyclo 3.1.0!hexane derivatives as intermediates in Processes for Producing Prostaglandins W. P. Schneider, Chem. Commun. 304 (1969); E. J. Corey, J. Amer, Chem. Soc., 94, 4014 (1972)!.
However, the yield obtained for the ring cleavage reaction of the cyclopropane ring is very low and furthermore, the reaction is not stereospecific.
Accordingly, this route is considered to be of less value as a practical method. Among these methods, processes which utilize 3-formylcyclopentanone derivatives as a starting material have been considered to be the most effective and broadly applicable methods for synthesis of natural and modified prostaglandins and derivatives thereof, e.g. prostanoids, which have similar structure and, in some cases have more selective and higher physiological activity than the natural products.
For the synthesis of 3-formylcyclopentanone derivatives, the following four methods have already been disclosed:
(1) the Michael addition of nitromethane to substituted cyclopentenones, followed by the Net reaction J. Bagli, et al., Tetrahedron Lett., 3815 (1972)!;
(2) the addition of hydrogen cyanide to cyclopentenone derivatives followed by reduction of the nitrile group M. P. L. Caton, et al., Tetrahedron Lett., 773 (1972)!;
(3) The conjugate addition of olefins to substituted cyclopentenones followed by ozonolysis of the olefin. F. S. Alvarez, et al., J. Amer. Chem. Soc., 94, 7823 (1972)!; and
(4) the utilization of the photochemical reaction product of tropolone as a starting material. P. Crabbe, et al., Tetrahedron Lett., 2215 (1975)!.
However, all of these methods have one or more of the following disadvantages: the starting materials are not easily available; the selectivity of the reaction is low; expensive or dangerous reagents are required; and the range of the suitable reaction conditions is narrow and thus reproducibility of the reaction is poor.
Accordingly, these methods cannot be employed in industrial processes.